Adult-onset immunodeficiency in Thailand and Taiwan

Sarah K. Browne, Peter D. Burbelo, Ploenchan Chetchotisakd, Yupin Suputtamongkol, Sasisopin Kiertiburanakul, Pamela A. Shaw, Jennifer L. Kirk, Kamonwan Jutivorakool, Rifat Zaman, Li Ding, Amy P. Hsu, Smita Y. Patel, Kenneth N. Olivier, Viraphong Lulitanond, Piroon Mootsikapun, Siriluck Anunnatsiri, Nasikarn Angkasekwinai, Boonmee Sathapatayavongs, Po Ren Hsueh, Chi Chang ShiehMargaret R. Brown, Wanna Thongnoppakhun, Reginald Claypool, Elizabeth P. Sampaio, Charin Thepthai, Duangdao Waywa, Camilla Dacombe, Yona Reizes, Adrian M. Zelazny, Paul Saleeb, Lindsey B. Rosen, Allen Mo, Michael Iadarola, Steven M. Holland

Research output: Contribution to journalArticlepeer-review

257 Citations (Scopus)

Abstract

BACKGROUND: Autoantibodies against interferon-γ are associated with severe disseminated opportunistic infection, but their importance and prevalence are unknown. METHODS: We enrolled 203 persons from sites in Thailand and Taiwan in five groups: 52 patients with disseminated, rapidly or slowly growing, nontuberculous mycobacterial infection (group 1); 45 patients with another opportunistic infection, with or without nontuberculous mycobacterial infection (group 2); 9 patients with disseminated tuberculosis (group 3); 49 patients with pulmonary tuberculosis (group 4); and 48 healthy controls (group 5). Clinical histories were recorded, and blood specimens were obtained. RESULTS: Patients in groups 1 and 2 had CD4+ T-lymphocyte counts that were similar to those in patients in groups 4 and 5, and they were not infected with the human immunodeficiency virus (HIV). Washed cells obtained from patients in groups 1 and 2 had intact cytokine production and a response to cytokine stimulation. In contrast, plasma obtained from these patients inhibited the activity of interferon-γ in normal cells. High-titer anti-interferon-γ autoantibodies were detected in 81% of patients in group 1, 96% of patients in group 2, 11% of patients in group 3, 2% of patients in group 4, and 2% of controls (group 5). Forty other anticytokine autoantibodies were assayed. One patient with cryptococcal meningitis had autoantibodies only against granulocyte-macrophage colony-stimulating factor. No other anticytokine autoantibodies or genetic defects correlated with infections. There was no familial clustering. CONCLUSIONS: Neutralizing anti-interferon-γ autoantibodies were detected in 88% of Asian adults with multiple opportunistic infections and were associated with an adult-onset immunodeficiency akin to that of advanced HIV infection. (Funded by the National Institute of Allergy and Infectious Diseases and the National Institute of Dental and Craniofacial Research; ClinicalTrials.gov number, NCT00814827.)

Original languageEnglish
Pages (from-to)725-734
Number of pages10
JournalNew England Journal of Medicine
Volume367
Issue number8
DOIs
Publication statusPublished - 2012 Aug 23

All Science Journal Classification (ASJC) codes

  • Medicine(all)

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